Increased prevalence of cytomegalovirus antibodies in homosexual men with syphilis: relation to sexual behaviour

Serum samples from 146 homosexual males, 40 heterosexual males and 51 females with at least one episode of syphilis were tested for the presence of IgG and IgM antibodies against cytomegalovirus (CMV IgG and CMV IgM). 100 blood donors served as a control group. CMV IgG was present in 95% of homosexual men compared with 68% of heterosexual men (p less than 0.001) and 73% of females (p less than 0.001) with past or present syphilis. CMV IgM was found in 43-68% of the venereal patients and with the highest percentage in homosexual men. Only 7% of blood donors had CMV IgM. It is concluded that CMV infection may be regarded as a venereal disease.     

Inhibition of gastric acid secretion by jejunal glucose and its relation to osmolality and glucose load

Intrajejunal infusion of hypertonic glucose and hypertonic saline inhibits pentagastrin-stimulated gastric acid secretion in man. This effect is generally ascribed to the hyperosmolality of the solutions. Five volunteers were given 50 g glucose in osmolar concentrations of 2700 mosmol/l and 900 mosmol/l, and five were given 25 g glucose in osmolar concentrations of 2700 mosmol/l and 300 mosmol/l. Control studies with intrajejunal infusion of physiologic saline were performed in all subjects. Median inhibition of gastric acid secretion was 91% after 50 g glucose and 47% after 25 g glucose and was unrelated to the osmolar concentration. These findings suggest that the acid-inhibitory effect of intrajejunally administered glucose is related to the glucose load and not to the osmolar concentration. Plasma responses of intact neurotensin, immunoreactivity, NH2-terminal neurotensin immunoreactivity, enteroglucagon, and gastric inhibitory polypeptide were all related to the amount of glucose given. Glucagon and somatostatin, both of which are potent inhibitors of gastric secretion, were not released by intrajejunally administered glucose.     

Human placental lactogen concentration during physiological fluctuations of serum glucose in normal pregnant and gestational diabetic women.

Oral glucose tolerance tests (OGTT) were carried out in 9 normal pregnant women and 11 non-obese gestational diabetics in late pregnancy. All samples were analysed for the content of glucose, insulin and placental lactogen hormone (HPL). Furthermore, spontaneous changes in the serum HPL concentration during a 3 h period were studied in 6 normal women in the 2nd half of pregnancy. During OGTT only small and insignificant changes in the level of HPL were observed in both the normal subjects and the gestational diabetics. Furthermore, the mean HPL concentration curves of the normal subjects and the gestational diabetics were superimposed although the mean glucose concentration curves were significantly different. The study of spontaneous changes in HPL revealed only small and insignificant fluctuations in the serum HPL level, and the mean concentration curve resembled those obtained from the OGTT-study. It is concluded that neither the absolute serum glucose level, nor physiological fluctuations in the serum glucose concentration seemed to influence the serum concentration of HPL in this type of patients.     

Complete histological regression of Kaposi's sarcoma following treatment with protease inhibitors despite persistence of HHV-8 in lesions

There is no current curative treatment for HIV-related Kaposi's sarcoma. The identification of human herpesvirus-8 as a possible aetiological agent suggests potential efficacy of anti-viral agents. We report here on the complete histological remission of Kaposi's sarcoma following treatment with protease inhibitors, even in patients with limited virological response and persistence of HHV-8.     

Metabolite ratios as potential biomarkers for type 2 diabetes: a DIRECT study

Aims/hypothesis

Circulating metabolites have been shown to reflect metabolic changes during the development of type 2 diabetes. In this study we examined the association of metabolite levels and pairwise metabolite ratios with insulin responses after glucose, glucagon-like peptide-1 (GLP-1) and arginine stimulation. We then investigated if the identified metabolite ratios were associated with measures of OGTT-derived beta cell function and with prevalent and incident type 2 diabetes.

Methods

We measured the levels of 188 metabolites in plasma samples from 130 healthy members of twin families (from the Netherlands Twin Register) at five time points during a modified 3 h hyperglycaemic clamp with glucose, GLP-1 and arginine stimulation. We validated our results in cohorts with OGTT data (n = 340) and epidemiological case–control studies of prevalent (n = 4925) and incident (n = 4277) diabetes. The data were analysed using regression models with adjustment for potential confounders.

Results

There were dynamic changes in metabolite levels in response to the different secretagogues. Furthermore, several fasting pairwise metabolite ratios were associated with one or multiple clamp-derived measures of insulin secretion (all p < 9.2 × 10^?7). These associations were significantly stronger compared with the individual metabolite components. One of the ratios, valine to phosphatidylcholine acyl-alkyl C32:2 (PC ae C32:2), in addition showed a directionally consistent positive association with OGTT-derived measures of insulin secretion and resistance (p ≤ 5.4 × 10^?3) and prevalent type 2 diabetes (OR_{Val_PC ae C32:2} 2.64 [β 0.97 ± 0.09], p = 1.0 × 10^?27). Furthermore, Val_PC ae C32:2 predicted incident diabetes independent of established risk factors in two epidemiological cohort studies (HR_{Val_PC ae C32:2} 1.57 [β 0.45 ± 0.06]; p = 1.3 × 10^?15), leading to modest improvements in the receiver operating characteristics when added to a model containing a set of established risk factors in both cohorts (increases from 0.780 to 0.801 and from 0.862 to 0.865 respectively, when added to the model containing traditional risk factors + glucose).

Conclusions/interpretation

In this study we have shown that the Val_PC ae C32:2 metabolite ratio is associated with an increased risk of type 2 diabetes and measures of insulin secretion and resistance. The observed effects were stronger than that of the individual metabolites and independent of known risk factors.

     

Acute renal effects of angiotensin converting enzyme inhibition in microalbuminuric type 1 diabetic patients

The renal effects of intravenous injection of 40 mg enalapril were investigated in 16 normotensive microalbuminuric type 1 (insulin-dependent) diabetic patients. After enalapril the following changes were observed: fractional albumin clearance ( Alb) decreased from 9.9 (3.0–23.8) to 8.2 (2.0–18.3)×10^–6 (2P<0.01); filtration fraction (FF) decreased from 0.260 (0.225–0.312) to 0.253 (0.190–0.297) (2P<0.01); renal plasma flow (RPF) increased from 565 (411–690) to 623 (449–785) (2P<0.01); and glomerular filtration rate (GFR) remained stable at 149 (128–181) versus 150 (124–185) ml · min^–1 (NS). These values were unchanged after placebo (n=8), except for RFP which decreased from 606 (401–701) to 559 (381–677) ml · min^–1 (2P<0.05) and GFR which was reduced from 148 (111–173) to 138 (111–167) (2P<0.05). A reduction in mean blood pressure from 94 (87–103) to 89 (79–101) mmHg (2P<0.05) was found in the enalapril group and a minor reduction in the placebo group from 97 (83–106) to 96 (81–104) mmHg (2P<0.05) was also noted. The relative changes in systolic blood pressure in the enalapril group correlated with changes in Alb (Spearman'sr=0.66, 2P<0.02) and FF (r=0.53, 2P<0.05). Acute inhibition of angiotensin converting enzyme does not reduce the pathological hyperfiltration in these patients and a reduction in Alb and FF can not be dissociated from the reduction in blood pressure.     

Inhibition of insulin receptor phosphorylation by peptides derived from major histocompatibility complex class I antigens

Peptides from the alpha 1 region (residues 61-85) of the D and K molecules of the major histocompatibility complex class I antigens inhibit insulin-induced tyrosine kinase activity of the purified human insulin receptors (IRs) as measured both by autophosphorylation and IR-mediated substrate [poly(Glu,Tyr)] phosphorylation. Half-maximal effect of the Dk-(61-85) peptide on IR autophosphorylation is obtained at 1.2 microM, and almost complete inhibition of IR kinase activity is obtained at 10 microM peptide. The corresponding K kappa-(61-85) peptide has a significantly weaker effect on autophosphorylation. No such effects are observed with nine peptides of similar length, but unrelated to major histocompatibility complex class I antigens. Neither of the major histocompatibility complex class I-derived peptides has any effect on the constitutively active kinase of a genetically engineered cytoplasmic IR domain. Further, insulin binding to IR is unaltered in the presence of the major histocompatibility complex class I-derived peptides. The inhibitory activity of the peptides on insulin-induced IR phosphorylation facilitated the observation that IRs require insulin to become substrate for an independent tyrosine kinase. In the presence of an inhibitory peptide, the constitutively active cytoplasmic IR kinase domain only phosphorylates the intact IR in the presence of insulin. We conclude that the tyrosine kinase activity of IRs may be altered by peptide interaction at an allosteric site and, moreover, IRs require insulin to assume a conformation permitting phosphorylation by an independent kinase.